New insights in cardiac structural changes in patients with Fabry's disease

Background Fabry's disease is on X-linked recessive genetic deficiency of t he enzyme cr-galactosidase leading to the pathologic intracellular depositi on of neutral glycosphingolipids. Although cardiac involvement is frequent, there is controversy regarding the character of the associated left ventri cular (LV) changes and the severity of valvular involvement. Methods clinical evaluation (disease severity scaling, laboratory tests, an d echocardiography) was performed in 13 hemizygous men (mean age 39 +/- 10 years) and 17 heterozygous women (mean age 35 +/- 19 years). Results LV hypertrophy (LVH) was frequent in subjects older than 30 years, more often in men (61%) than in women (18%, P < .001). The degree of LVH wa s independently associated with age and the logarithm of alpha-galactosidas e activity (r(2) = 0.70, P < .001). The predominant IV geometric patterns w ere concentric LVH and remodeling, both present in 11 subjects (36%). Three patients had an asymmetric septal hypertrophy mimicking hypertrophic cardi omyopathy. In most subjects with LVH, the systolic function was normal and severe diastolic dysfunction (restrictive pattern) was not noted. Minor str uctural abnormalities of the mitral valve were found in 17 subjects (57%). The aortic valve was affected in 14 patients (47%). Valvular abnormalities were frequently accompanied by regurgitation of minor to mild degree. The p resence of LVH or valvular changes was associated with increased disease se verity. Conclusions Echocardiographically detectable cardiac involvement is frequen t with Fabry's disease, particularly in older subjects, and more pronounced in affected hemizygous men than in heterozygous women. LVH is frequently o bserved but usually not associated with significant systolic or restrictive diastolic dysfunction. Concentric LVH and remodeling appear to be the majo r manifestations of LV structural alteration. The frequently noted valvular abnormalities were not associated with a significant degree of regurgitati on. Valvular and especially LV structural changes may serve as a useful mar ker of disease severity.